Preparation of c-acetylated compounds



Patented Mar. 11, 194i PREPARATION OF C-ACETYLATED COMPOUNDS John A. Spence and Edward F. Degering, West Lafayette, Ind., assignors to Purdue Research Foundation, La Fayette, 12111., a corporation of Indiana No Drawing. Application August 30, 1945,

Serial No. 613,698

This invention relates to the preparation of C- acetylated compounds.

We have shown that fi-diketones and fl-ketoesters can be converted to enol acetates by condensing the B-diketones or ,B-ketoesters with ketene in the presence of an acid catalyst, such as an acid catalyst of the general formula:

X-SOa-OH wherein X represents a hydroxyl group, an organic group containing a non-metallic atom in addition to carbon and hydrogen, the X group being linked to the S atom through said nonmetallic atom, or an inorganic group consisting of non-metallic atoms other than carbon, for example sulfuric acid, chlorosulfonic acid, alkylsulfuric acids, sulfamic acid, dimethylsulfamic acid, oleum, fluorosulfonic acid, N-acetylsulfamic acid, etc. See our copending applications Serial Nos. 556,886 and 556,887, each filed October 2, 1944 (now United States Patents 2,407,301 and 2,407,302, each dated September 10, 1946) of each of which the instant application is a continuation-in-part.

We have now found that ketene (CH2=C=O) reacts with compounds containing a group to give C-acetylated derivatives. rather than unsaturated esters.

Our new process is an improvement over the known processes for preparing C-acetylated de rivatives of ketoesters containing a.

group, i. e. the processes involving treatment.of the sodium derivative of a ketoester containing a- CO-CH2-CO- group with acetyl chloride or acetic anhydride, in that our new process gives a much smaller amount of the O-acetyiated derivative as side-reaction product; in fact the O- acetylated derivatives produced in our new process are usually practically negligible- It is, accordingly, an object of our invention to provide a process for C-acetylating compounds containing a -COCI-Iz-CO- group. A further object is to provide new compounds. Other objects will become apparent hereinafter.

In accordance with our invention, we react ketene (CI-Iz=C=O) witha compound containing a --CO-CH?-CO- group. The reaction takes place without a catalyst, although the use of catalysts is within the purview of our invention.

Salenic acid (HzseOi) may exert a slight catalytic action in some cases. Among other com- 8 Claims. (01. 260-483) pounds containing a COCH2-CO- group, those represented by the following general formula are well suited for use in our invention.

wherein R and R each represents a member se-' lected from the group consisting of an alkyl group, an aralkyl group, .an aryl group, an alkoxyl group and an aryloxyl group. Typical examples of the compounds represented by the foregoing general formula I are: fl-diketones (for instance acetylacetone, 2,4-hexanedione, 2,4-heptanedione, 5-methyl-2,4-hexaneclione, acetylacetophenone, i. e. benzoylacetone, dibenzoylmethane, propionylacetophenone, nand isobutyrylacetophenone and acetylmethylbenzyl ketone, i. e. 1-phenyl-2,4-pentanedione), fl-ketoesters (for instance methyl acetoacetate, ethyl acetoacetate, benzyl acetoacetate, ethyl propionacetate, methyl n-butyroacetate phenyl acetoacetate, ethyl-benzoylacetate and ethyl decanoylacetate) and malonic esters (for instance dimethyl malonate, diethyl malonate,'di-n-propyl malonate, di-n-butyl malonate, dibenzyl malonate, diphenyl malonate, and methyl ethyl malonate).

In practicing our invention, the compound containing the CO--CH2CO-- group is placed in a reaction vessel. The compound is then raised to reaction temperature and ketene (CH2=C=O) preferably freshly prepared, is added to the compound at a rate which substantially precludes the building up in the reaction mixture of any substantial quantity of unreacted ketene. The dispersion of the ketenc in the reaction mixture is advantageously facilitated by agitation of the reaction mixture. Agitation also aids in avoiding local over-heating of the reaction mixture. The addition of ketene is advantageously continued until a quantity has been added which is at least as much as the molecular equivalent of the quantity of the compound containing'the group which is present, or until no further reac- C. at 19 mm. Hg

a wide temperature range. Usually we have found that the reaction takes place at an appreciable rate at from about 60 to about 130 6., although higher or lower weight compounds containing a --CO-CH2-CO- order to avoid pound. The heat of reaction may require cooling of the reaction mixture to control the temperature within the desired range.

If desired a reaction medium which is inert to the ketene and the compound containing the group, e. g. a saturated aliphatic hydrocarbon or an aromatic hydrocarbon, can be employed. However, a reaction medium is unnecessary in the case of most compounds containing a group which are liquid at the reaction temperature employed.

while stirring the reaction mixture. At the end 40 of this time, the dark reaction liquor was removed and shaken with a littlesodium acetate and allowed to stand for about 12 hours. The liquor was then filtered, and the filtered liquor subjected to distillation under reduced pressure. The clear distillate was then fractionated through a small Podbielniak column. ml. of acetylacetone were recovered. 45 ml. (80 per cent conversion) of triacetylmethane, boiling at 100-104" pressure, were obtained. The following tabulation ShOWs the results of still further preparations of triacetylmethane by our process:

Aeetyl- Selenic Temp.

acetone acid +5 Moln Grams C. m. 0.5 75 35 0.5 None 80 34 0.5 1.2 105 45 0.5 None 105 45 From these results, it does not appear that selenic acid catalyzes the reaction. In a similar manner the following fi-diketones can be converted into C-acetylated compounds:

7 p-diketone C-ecetylated compound Diawyipmpimtmethaua.

I .Dueetyl-n-ontyrylmethane: r 5-methyl-2,4-bexan Diacetyllsobutyrylmethane. Acetylaeetopheno e Diacetylbenzoylmethane. Pr0pi0nylacet0phen0ne.... Acetylbenzoylpropionylmethane. n--Butyryleeetophenone. Aoetylbenzeyl-n-butyrylmethane. Isobutyrylaoetophenone. Acetylbenzoylisobutyrylmethane. Aeetylmethylbenzylketone Diaeetylpbenylaeetylmetbane.

temperatures can be employed. Especially with the higher molecular higher temperatures should be avoided in.

thermal decomposition of the com practicing our invention:

Example 2.-Diacetylcarbethoarymethane (ethyl a-acetylacetoacetate) CHaCO CHaCO-CH C2H5OOC "One'mole of ethyl acetoacetate (130 g.) .;.was

placed in a reaction vessel together with 0.7 g. of

selenic acid. .The reaction vessel was immersed in an electricallyheat'ed oil bath and the Com tents of the vessel maintained at C.i5. .Ke-

time (2.25 moles), generated by the pyrolysis of acetone, was passed into theheated ethyl acetoacetate-selenic acid mixture over a period of about 3 hours. The resulting dark liquor was removed from the reaction vessel, treated with a little sodium acetate and filtered. The filtered liquor was distilled under reduced pressure and 125 ml. per cent conversion) of diacetylcarbethoxymethane, boiling at -90 C. at 10 mm. of Hg pressure, were obtained. The following tabulation shows the results of still further preparations of diacetylcarbethoxymethane by our process:

Ethyl aoeto- Selenic 'lem acetate acid i=5 Yield Moles Grams 0. M1. 0.5 7. 5 0. 5 one 130 3. 0 0.5 1. 2 4. 0 l. 0 0. 7 75 125.0 1. 0 None 80 106.0 0.5 "'75 32.0

l 1 gram of sodium acetate instead of selenic acid was used.

From these data it appears that selenic acid has a slight catalytic effect on the reaction. In a similar manner the following p-ketoesters can be converted into C-acetylated compounds:

7 reaction vessel.

B-ketoester 'C-acetylated compound Methylacetoacetate. Dincetylcarbmethoxymethane. Benz laeetoaoetate Diaoetylcarb henylmethoxymethane. Eth ropionoacetate Aoetylcarbet 0x ropionylmethane.

Aoetyl-n-butyry carbmethoxymethane. Diacetylcarb henoxymethane. Acetylcarbet oxydecanoylmethanc.-

Met y n-butyroacetatc.. Phen lacetoacetate Ethy decanoylaeetate.-

Example 3.-Acetyldicarbethoxymethane (acetyle diethylmalonate) cane 0 0-03 One-half mole of diethyl malonate (80 g.) and 1 g. of selenic acid (sp. g. 1.4) were placed in a The reaction vessel was placed in an electrically heated oil bath and the tents of thevessel maintained at 100 C.:5. Ketene (about diagrams};, gerrerateg y the;, pyrolysis of acetone, was passed into the malonate-selenic acidmixture over a period of 2 hours. At the end of this time, the dark reaction liquor was shaken with a little sodium acetate and allowed to stand for about 12 hours. It was then filtered and distilled under reduced pressure. 7.5 ml; of acetyldicarbethoxymethane, boiling at -123 C. at 18 mm. of Hg pressure, were obtained when the distillate was rectified with a small Podbielniak column. In a similar manner ated diethyl 5 the following malonates can be converted into C-acetylated compounds! Malonate C-aoetylated compound Acetyldicarbmcthoxymethane. Acetyldicarb-n-gropoxymethane. Acctyldicarb-nutoxymethane. Acetyldicarbphenoxymethane.

Dimethyl malonate Di-nropylmalonate. Di-nutyl malonate Diphenyl malonate.

Dibenzyl malonate I Ac'etyldicarbphenylmethoxymethane.

Example 4.-Acetyldibenzoylmethane (p-jorm) CoHaC 0-0 H CaHlO 0 zoylmethane were obtained (M. P. 80-85" C. sci-- tens; 107-l15 C. melts). This range of melting point is owing to an equilibrium between the onand p-forms of acetyldibenzoylmethane. The yield of p-acetyldibenzoylmethane was 66 per cent.

' Example 5.-Acetylbenzoylcarbethozcymethane (ethyl-a-acetylbenzoylacetate) CHsC O cmc OCH C2H5C o 0 Ketene (1.2 moles) was passed into 96 g. (0.5 mole) of ethyl benzoylacetate over a period of 2 hours, at 80 0x5; while thoroughly agitating the ethylbenzoylacetate. The resulting dark reaction liquor was distilled from a Claisen flask at reduced pressure. '71 g. of acetylbenzoylcarbethoxymethane, boiling at 148 to 156 C. at 5 mm. of Hg pressure, were obtained. This material was soluble in dilute alkali and gave a blue copper salt. g

In a. manner similar to that illustrated in the foregoing examples, other compounds containing a --COCH2CO group can be C-acetylated. Small amounts of water can be present in the reaction mixtures without adversely affecting the process.

What we claim and desire Letters Patent of the United is:

to be secured by States of America 1. In a process for preparing C-acetylated compounds or the following general formula:

wherein R and R each represents; a member selected from the group consisting of an alkyl group, an aralkyl group, an aryl group, an alkoxyl group and an aryloxyl group, the step which comprises reacting ketene (CI-I2=C=O) with a carbonyl compound selected from the group of compounds represented by the following general formula:

wherein R and R each represents a member selected from the group consisting of an alkyl group, an aralkyl group, an aryl group, an alkoxyl group and an aryloxyl group, the carbonyl C., while agitating ants present.

- resents an alkoxyl group,

'wherein R and R 2. In a process for preparing C-acetylatecl compounds of the following general formula:

0 R-OO-H-CO-R wherein R and R each represents an alkyl'group, the step which comprises reacting ketene (CH2=C=O) with a p-diketone selected from the group of p-diketones represented by the following general formula:

wherein R and R each represents an alkyl group, the ,B-diketone and the ketene being .the sole re" actants present.

3. In a process for preparing triacetylmethane, the step which comprises ketene (CHz=C=-O3 with acetylacetone, the acety'lacetone and the ketene being the sole reactants present.

4. In a process for preparing C-acetylated compounds of the following general formula:

CHI

0 R-CO-JJH-CO-R wherein R represents an alkyl group and R resents an alkoxyl group, prises condensing ketene (CH2=C=O) with a p-ketoester selected from the group of fi-ketoesters represented by the following general formula:

rep the step which com-a R-CO-CHz-CO-R wherein R represents an alkyl group and R the fi-ketoester and-the ketene being the sole reactants present.

5. In a process for preparing diacetylcarbethoxymethane, the step which comprises reacting ketene (CHz'=C=O) with ethylacetoacetate, the ethylacetoacetate and the ketene being the sole reactants present.

6. In a process for preparing C-acetylated compounds of the following general formula:

. CE: I

o a-oo-n-oo-n' wherein R and R' each represents an alkoxyl group, the step which comprises reacting ketene (CH2=C=O) with a malonic ester selected from the group of malonic following general formula:

each represents an alkoxyl roup, the malonic the sole reactants present.

7. In a process for preparing acetyldicarbethoxymethane, the step which comprises reacting ketene (CH2=C=O) with diethylmalonate, the diethylmalonate and the ketene being the sole reactants present.

8. In a process for preparing C-acetylated compounds of the following general formula:

group, an aralkyl group, an aryl group, an alrepesters represented by the ester and the ketene being n koxyl group and an aryloxyl group, the step which comprises reacting, in an inert reaction medium, ketene (CHzfiO) with a carbonyl compound selected from the group of compounds represented by the following general formula:

wherein R and R each represents a, member selected from the group consisting of an alkyl group,'an aralkyl group, an aryl group, an alkoxyl group and an aryloxyl group, the carbonyl compound and the ketene being the sole reactants present.

JOHN A. SPENCE. EDWARD F. DEGERING.

REFERENCES CITED 'Ihe following references are of record in the file of this patent:

FOREIGN PATENTS Number Country Date 666,703 French Oct. 4, 1929 10 OTHER REFERENCES Gwynn et aL, J ourn. Am. Chem. Soc, vol. 64 (1942) pp. 2216-2218. 

